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1.
Antibiotics (Basel) ; 13(4)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38667048

RESUMO

Gentamicin, an aminoglycoside antibiotic, is a mixture of therapeutically active C1, C1a, C2 and other minor components. Despite its decades-long use in pigs and other species, its intramuscular (IM) pharmacokinetics/pharmacodynamics (PKs/PDs) are unknown in piglets. Furthermore, the PKs of many drugs differ between healthy and sick animals. Therefore, we investigated the PKs of gentamicin after a single IM dose (10 mg/kg) in healthy piglets and piglets that were intranasally co-infected with Actinobacillus pleuropneumoniae and Pasteurella multocida (PM). The plasma concentrations were measured using validated liquid chromatography/mass spectrometry. The gentamicin exposure was 36% lower based on the area under the plasma concentration-time curve and 16% lower based on the maximum plasma concentration (Cmax) in the infected piglets compared to the healthy piglets, while it was eliminated faster (shorter half-life and larger clearance) in the infected piglets compared to the healthy piglets. The clearance and volume of distribution were the highest for the C1 component. C1, C1a and C2 accounted for 22-25%, 33-37% and 40-42% of the total gentamicin exposure, respectively. The PK/PD target for the efficacy of aminoglycosides (Cmax/minimum inhibitory concentration (MIC) > 10) could be exceeded for PM, with a greater magnitude in the healthy piglets. We suggest integrating this PK information with antibiotic susceptibility data for other bacteria to make informed antibiotic and dosage regimen selections against piglet infections.

2.
Environ Sci Technol ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38629715

RESUMO

Plastic contamination is a global pervasive issue, extending from coastal areas and open oceans to polar regions and even the deep sea. Microplastic (MP) contamination in hydrothermal vents, which are known for their high biodiversity even under extreme conditions, has remained largely unexplored. Here, we present, for the first time, MP pollution in a deep-sea hydrothermal vent at one of the biodiversity hotspots─the Central Indian Ridge. Not only the environment (seawater: 2.08 ± 1.04 MPs/L, surface sediments: 0.57 ± 0.19 MP/g) but also all six major benthic species investigated were polluted by MPs. MPs mainly consisted of polypropylene, polyethylene terephthalate, and polystyrene fragments ≤100 µm and were characterized as being either transparent or white in color. Remarkably, bioaccumulation and even biomagnification of microplastics were observed in the top predators of the ecosystem, such as squat lobsters (14.25 ± 4.65 MPs/individual) and vent crabs (14.00 ± 2.16 MPs/individual), since they contained more MPs than animals at lower trophic levels (e.g., mussels and snails, 1.75-6.00 average MPs/individuals). These findings reveal MP contamination of an ecosystem in a hydrothermal vent, thereby suggesting that their accumulation and magnification can occur in top-level animals, even within remote and extreme environments.

3.
J Phys Chem A ; 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651558

RESUMO

We propose a new perturbation theory framework that can be used to help with the projective solution of the Schrödinger equation for arbitrary wave functions. This Flexible Ansatz for N-body Perturbation Theory (FANPT) is based on our previously proposed Flexible Ansatz for the N-body Configuration Interaction (FANCI). We derive recursive FANPT expressions, including arbitrary orders in the perturbation hierarchy. We show that the FANPT equations are well-behaved across a wide range of conditions, including static correlation-dominated configurations and highly nonlinear wave functions.

4.
J Chem Phys ; 160(16)2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38651814

RESUMO

HORTON is a free and open-source electronic-structure package written primarily in Python 3 with some underlying C++ components. While HORTON's development has been mainly directed by the research interests of its leading contributing groups, it is designed to be easily modified, extended, and used by other developers of quantum chemistry methods or post-processing techniques. Most importantly, HORTON adheres to modern principles of software development, including modularity, readability, flexibility, comprehensive documentation, automatic testing, version control, and quality-assurance protocols. This article explains how the principles and structure of HORTON have evolved since we started developing it more than a decade ago. We review the features and functionality of the latest HORTON release (version 2.3) and discuss how HORTON is evolving to support electronic structure theory research for the next decade.

5.
Sci Rep ; 14(1): 8747, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627483

RESUMO

This study aimed to evaluate the incidence and likelihood of antibiotic-associated encephalopathy (AAE), comparing rates among the classes of antibiotics in monotherapy or in combination therapy. We also investigated the associations between the incidence of AAE and the glomerular filtration rate (GFR) and electroencephalogram features. Consecutive admissions that used any kind of antibiotics to treat infectious diseases were identified from six hospitals. We classified antibiotics according to three distinct pathophysiologic mechanisms and clinical subtypes. We searched for the incidence of AAE as the primary outcome. A total of 97,433 admission cases among 56,038 patients was identified. Cases that received type 1 antibiotics had significantly more frequent AAE compared to those that received type 2 antibiotics (adjusted odds ratio [OR], 2.62; 95% confidence interval [CI] 1.15-5.95; P = 0.021). Combined use of type 1 + 2 antibiotics was associated with a significantly higher incidence of AAE compared to the use of type 2 antibiotics alone (adjusted OR, 3.44; 95% CI 1.49-7.93; P = 0.004). Groups with GFR < 60 mL/min/1.73 m2 had significantly higher incidence rates of AAE compared to those with GFRs ≥ 90 mL/min/1.73 m2 among cases that received type 1 + 2 antibiotics. Detection of spike-and-wave or sharp-and-wave patterns on electroencephalogram was significantly more common in the combination therapy group. Combination use of antibiotics was associated with a higher incidence of AAE compared to monotherapy. The incidence of AAE significantly increased as renal function decreased, and epileptiform discharges were more likely to be detected in cases receiving combined antibiotics.


Assuntos
Antibacterianos , Encefalopatias , Humanos , Antibacterianos/efeitos adversos , Incidência , Taxa de Filtração Glomerular , Encefalopatias/induzido quimicamente , Encefalopatias/epidemiologia , Encefalopatias/tratamento farmacológico , Hospitais
6.
Integr Comp Biol ; 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599630

RESUMO

Limitations on energetic resources create evolutionary trade-offs, prompting us to investigate if investment in claw strength remains consistent across crustaceans living in diverse habitats. Decapod crustaceans living in deep-sea hydrothermal vents are ideal for this study due to their extreme environment. In this study, we investigated whether decapods (blind crab Austinograea sp. and the squat lobster Munidopsis lauensis) living in deep-sea hydrothermal vents prioritize investing in strong claws compared to the carapace, like coastal decapods. We analyzed exoskeleton morphology, mechanical properties, structures, and elemental composition in both the carapace and claws of four Decapoda species (two each from Brachyura and Anomura infraorders) in vent and coastal habitats. Coastal decapods had approximately 4 to 9 times more teeth on their claw cutting edge than the vent species. Further, only the coastal species exhibited higher firmness in their claws than in their carapaces. Each infraorder controlled exoskeletal hardness differently: Brachyura changed the stacking height of the Bouligand structure, while Anomura regulated magnesium content in the exoskeleton. The vent decapods may prioritize strengthening their carapace over developing robust claws, allocating resources to adapt to the harsh conditions of deep-sea hydrothermal vents. This choice might enhance their survival in the extreme environment, where carapace strength is crucial for protecting internal organs from environmental factors, rather than relying on the powerful claws seen in coastal decapods for a competitive advantage.

7.
J Chem Phys ; 160(14)2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38597308

RESUMO

Electron pairs have an illustrious history in chemistry, from powerful concepts to understanding structural stability and reactive changes to the promise of serving as building blocks of quantitative descriptions of the electronic structure of complex molecules and materials. However, traditionally, two-electron wavefunctions (geminals) have not enjoyed the popularity and widespread use of the more standard single-particle methods. This has changed recently, with a renewed interest in the development of geminal wavefunctions as an alternative to describing strongly correlated phenomena. Hence, there is a need to find geminal methods that are accurate, computationally tractable, and do not demand significant input from the user (particularly via cumbersome and often ill-behaved orbital optimization steps). Here, we propose new families of geminal wavefunctions inspired by the pair coupled cluster doubles ansatz. We present a new hierarchy of two-electron wavefunctions that extends the one-reference orbital idea to other geminals. Moreover, we show how to incorporate single-like excitations in this framework without leaving the quasiparticle picture. We explore the role of imposing seniority restrictions on these wavefunctions and benchmark these new methods on model strongly correlated systems.

8.
Exp Brain Res ; 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38563977

RESUMO

Reach-to-grasp actions are fundamental to the daily activities of human life, but few methods exist to assess individuals' reaching and grasping actions in unconstrained environments. The Block Building Task (BBT) provides an opportunity to directly observe and quantify these actions, including left/right hand choices. Here we sought to investigate the motor and non-motor causes of left/right hand choices, and optimize the design of the BBT, by manipulating motor and non-motor difficulty in the BBT's unconstrained reach-to-grasp task. We hypothesized that greater motor and non-motor (e.g. cognitive/perceptual) difficulty would drive increased usage of the dominant hand. To test this hypothesis, we modulated block size (large vs. small) to influence motor difficulty, and model complexity (10 vs. 5 blocks per model) to influence non-motor difficulty, in healthy adults (n = 57). Our data revealed that increased motor and non-motor difficulty led to lower task performance (slower task speed), but participants only increased use of their dominant hand only under the most difficult combination of conditions: in other words, participants allowed their performance to degrade before changing hand choices, even though participants were instructed only to optimize performance. These results demonstrate that hand choices during reach-to grasp actions are more stable than motor performance in healthy right-handed adults, but tasks with multifaceted difficulties can drive individuals to rely more on their dominant hand.

9.
Vet Med (Praha) ; 69(1): 8-17, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38465002

RESUMO

Asian sand dust (ASD), also called China dust or yellow dust, mainly occurs in East Asia during spring and autumn. Because ASD enters the body mainly through the respiratory system, it can cause respiratory disorders or worsen underlying diseases. Because of this, it has become an important health concern that threatens the well-being of humans and animals. In this study, we investigated the effects of 15 and 30 mg/kg of Pycnogenol (PYC15 and 30 groups), a pine bark extract, on ASD-induced pulmonary inflammation in mice. We evaluated the inflammatory cell counts, inflammatory cytokines, and matrix-metalloproteinase (MMP)-9 expression in animal models. PYC administration significantly decreased inflammatory cell infiltration into lung tissue; this was accompanied by a reduction in the levels of proinflammatory mediators including interleukin (IL)-1ß (P < 0.01), IL-6 (P < 0.01) and tumour necrosis factor-α (P < 0.01) in bronchoalveolar lavage fluids of ASD-exposed mice (ASD group). Histological analysis revealed that PYC suppressed ASD-induced pulmonary inflammation. Moreover, PYC suppressed the levels of matrix-metalloproteinase (MMP)-9 in the lung tissue of ASD-exposed mice, indicating that PYC reduced ASD-induced pulmonary inflammation by suppressing MMP-9. Together, these results indicate that PYC as the potential to treat ASD-driven pulmonary inflammation.

10.
J Ginseng Res ; 48(2): 181-189, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465217

RESUMO

Background: Cigarette smoke is generally accepted as a major contributor to chronic obstructive pulmonary disease (COPD), which is characterized by emphysematous lesions. In this study, we investigated the protective effects of Korean Red Ginseng (KRG) against cigarette smoke condensate (CSC)-induced emphysema. Methods: Mice were instilled with 50 mg/kg of CSC intranasally once a week for 4 weeks, KRG was administered to the mice once daily for 4 weeks at doses of 100 or 300 mg/kg, and dexamethasone (DEX, positive control) was administered to the mice once daily for 2 weeks at 3 mg/kg. Results: KRG markedly decreased the macrophage population in bronchoalveolar lavage fluid and reduced emphysematous lesions in the lung tissues. KRG suppressed CSC-induced apoptosis as revealed by terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling staining and Caspase 3 immunohistochemistry. Additionally, KRG effectively inhibited CSC-mediated activation of Bcl-2-associated X protein/Caspase 3 signaling, followed by the induction of cell survival signaling, including vascular endothelial growth factor/phosphoinositide 3-kinase/protein kinase B in vivo and in vitro. The DEX group also showed similar improved results in vivo and in vitro. Conclusion: Taken together, KRG effectively inhibits macrophage-mediated emphysema induced by CSC exposure, possibly via the suppression of pro-apoptotic signaling, which results in cell survival pathway activation. These findings suggest that KRG has therapeutic potential for the prevention of emphysema in COPD patients.

11.
Mar Pollut Bull ; 200: 116107, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38330812

RESUMO

The anthropogenic construction activities on the coasts, such as pile-driving, generate vibrations that propagate through the substrate. Such substrate-borne vibrations could potentially affect marine organisms inhabiting the benthic environments. However, there is a lack of documented studies on the effects of vibrations on benthic animals. To investigate whether anthropogenic substrate-borne vibrations such as pile-driving operation influence the fiddler crab, Austruca lactea, we measured their locomotion response under vibrations of 35, 120, 250, 500, and 750 Hz generated by a vibrator. We compared the locomotion of crabs between control and vibration-treatment groups using videography. The duration of movements was significantly lower under 120 Hz vibrations compared to the control. Moreover, crab velocity was significantly higher under vibrations of 120 Hz and 250 Hz compared to the control group. Our result suggests that A. lactea can detect low-frequency substrate-borne vibrations and experience stress, leading to increased energy consumption.


Assuntos
Braquiúros , Animais , Braquiúros/fisiologia , Vibração , Organismos Aquáticos , Locomoção/fisiologia
12.
J Couns Psychol ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38358676

RESUMO

Vocational psychologists have called for greater attention to different forms of capital, any resource or asset that confers profit and power, to better understand the vocational development process, particularly for those who lack resources and power. However, previous research has had several conceptual and measurement limitations, such as the use of less inclusive frameworks; a focus on more privileged populations; and the overuse of categorical, dummy coded, and objective measures. To address these limitations, the present study aimed to (a) develop an inclusive, subjective, continuous, and multidimensional work capital scale and (b) validate the new scale with representative samples of working adults and job seekers across two studies. We developed a 16-item four-factor Work Capital Scale that consists of Economic Work Capital, Human Work Capital, Social Work Capital, and Cultural Work Capital. Scores from the Work Capital Scale were invariant across household income, social class, gender, race, and employment status. We found that the correlational model fit best to the data and provided evidence for convergent and divergent validity by relating the subscales to subjective social class, objective socioeconomic indicators, and existing measures of capital. The present study advances theory and research in work capital and provides a tool for practitioners to use. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

13.
J Psychosom Res ; 179: 111618, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38412653

RESUMO

BACKGROUND: The objectives of this cross-sectional study were to explore the relationship between weekend catch-up sleep (WCUS) and the risk of prediabetes/diabetes and to assess how this risk varies based on WCUS duration, using a large population sample in South Korea. METHODS: Data were sourced from the 2021 Korea National Health and Nutrition Examination Survey, involving 2472 subjects aged 30 years and above, employed, and not using blood glucose-lowering medications. Prediabetes/diabetes risk was examined based on the presence of WCUS. Participants were categorized into four groups by WCUS duration (< 1, ≥ 1 and < 2, ≥ 2 and < 3, and ≥ 3 h) to evaluate the prediabetes/diabetes risk across varying WCUS durations. RESULTS: No significant difference in prediabetes/diabetes risk was observed between the WCUS and non-WCUS groups. In subgroup analysis, a WCUS duration of 1 to 2 h was related to a lower odds ratio of prediabetes (aOR = 0.618, 95% CI = 0.382-0.999), while 3 h or more was associated with a higher odds ratio of diabetes (aOR = 3.098, 95% CI = 1.561-6.149). CONCLUSIONS: In individuals who experience insufficient sleep during weekdays and manage to achieve the optimal average sleep duration of 1 to 2 h of WCUS, WCUS was associated with improved blood glucose regulation. However, compensating for excessive weekday sleep deprivation with WCUS of 3 h or more was associated with impaired blood glucose regulation.


Assuntos
Estado Pré-Diabético , Humanos , Estado Pré-Diabético/epidemiologia , Estudos Transversais , Glicemia , Inquéritos Nutricionais , Sono/fisiologia , Privação do Sono/complicações
14.
Neurorehabil Neural Repair ; 38(2): 134-147, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38268466

RESUMO

BACKGROUND: Little is known about how peripheral nerve injury affects human performance, behavior, and life. Hand use choices are important for rehabilitation after unilateral impairment, but rarely measured, and are not changed by the normal course of rehabilitation and daily life. OBJECTIVE: To identify the relationship between hand use (L/R choices), motor performance, and patient-centered outcomes. METHODS: Participants (n = 48) with unilateral peripheral nerve injury were assessed for hand use via Block Building Task, Motor Activity Log, and Edinburgh Handedness Inventory; dexterity (separately for each hand) via Nine-Hole Peg Test, Jebsen Taylor Hand Function Test, and a precision drawing task; patient-centered outcomes via surveys of disability, activity participation, and health-related quality of life; and injury-related factors including injury cause and affected nerve. Factor Analysis of Mixed Data was used to explore relationships between these variables. The data were analyzed under 2 approaches: comparing dominant hand (DH) versus non-dominant hand (NH), or affected versus unaffected hand. RESULTS: The data were best explained by 5 dimensions. Good patient outcomes were associated with NH performance, DH performance (separately and secondarily to NH performance), and preserved function and use of the affected hand; whereas poor patient outcomes were associated with preserved but unused function of the affected hand. CONCLUSION: After unilateral peripheral nerve injury, hand function, hand usage, and patient life arise from a complex interaction of many factors. To optimize rehabilitation after unilateral impairment, new rehabilitation methods are needed to promote performance and use with the NH, as well as the injured hand.


Assuntos
Traumatismos dos Nervos Periféricos , Humanos , Qualidade de Vida , Mãos , Extremidade Superior , Lateralidade Funcional/fisiologia
15.
Mar Pollut Bull ; 200: 116052, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290361

RESUMO

Continuous emissions of anthropogenic CO2 are changing the atmospheric and oceanic environment. Although some species may have compensatory mechanisms to acclimatize or adapt to the changing environment, most marine organisms are negatively influenced by climate change. In this study, we aimed to understand the compensatory mechanisms of the Antarctic clam, Laternula elliptica, to climate-related stressors by using archived shells from 1995 to 2018. Principal component analysis revealed that seawater pCO2 and salinity in the Antarctic Ocean, which have increased since the 2000's, are the most influential factors on the characteristics of the shell. The periostracum thickness ratio and nitrogen on the outermost surface have increased, and the dissolution area (%) has decreased. Furthermore, the calcium content and mechanical properties of the shells have not changed. The results suggest that L. elliptica retains the mechanism of protecting the shell from high pCO2 by thickening the periostracum as a phenotype plasticity.


Assuntos
Bivalves , Água do Mar , Animais , Concentração de Íons de Hidrogênio , Acidificação dos Oceanos , Oceanos e Mares , Regiões Antárticas , Exoesqueleto , Dióxido de Carbono
16.
J Ginseng Res ; 48(1): 52-58, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38223821

RESUMO

Background: Skeletal muscle denervation leads to motor neuron degeneration, which in turn reduces muscle fiber volumes. Recent studies have revealed that apoptosis plays a role in regulating denervation-associated pathologic muscle wasting. Korean red ginseng (KRG) has various biological activities and is currently widely consumed as a medicinal product worldwide. Among them, ginseng has protective effects against muscle atrophy in in vivo and in vitro. However, the effects of KRG on denervation-induced muscle damage have not been fully elucidated. Methods: We induced skeletal muscle atrophy in mice by dissecting the sciatic nerves, administered KRG, and then analyzed the muscles. KRG was administered to the mice once daily for 3 weeks at 100 and 400 mg/kg/day doses after operation. Results: KRG treatment significantly increased skeletal muscle weight and tibialis anterior (TA) muscle fiber volume in injured areas and reduced histological alterations in TA muscle. In addition, KRG treatment reduced denervation-induced apoptotic changes in TA muscle. KRG attenuated p53/Bax/cytochrome c/Caspase 3 signaling induced by nerve injury in a dose-dependent manner. Also, KRG decreases protein kinase B/mammalian target of rapamycin pathway, reducing restorative myogenesis. Conclusion: Thus, KRG has potential protective role against denervation-induced muscle atrophy. The effect of KRG treatment was accompanied by reduced levels of mitochondria-associated apoptosis.

17.
Poult Sci ; 103(1): 103147, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37931394

RESUMO

Lincomycin (LCM) is an antibiotic used to treat severe bacterial infections in livestock and companion animals. In this study, we aimed to investigate the oral bioavailability of LCM with PK data after IV and PO administration and to compare differences in drug residue patterns in eggs. To ensure food safety, an additional study on egg residue was conducted using 3 different commercial LCM drugs. For bioavailability study, laying hens were divided into oral and intravenous (n = 8/group) groups and received single dose (10 mg/kg) of LCM. The limits of quantification for LCM were 0.729 µg/mL and 0.009 mg/kg in plasma and eggs, respectively. The oral group exhibited a significantly lower average serum drug concentration than the IV group, with a bioavailability of 2.6%. Furthermore, the egg residue profiles confirmed reduced systemic drug exposure after oral administration. For the commercial LCM drug egg residue experiment, laying hens were divided into low- and high-dose groups (n = 12/group) for each drug and treated with the recommended dosage and administration method for each respective drug. The eggs were collected and analyzed until 14 d after the last drug treatment. Despite differences in the LCM content and formulation among commercial drugs, all the tested commercial drugs showed average concentrations below the MRL in eggs within approximately 3 d after the last drug treatment. In this study, we have confirmed that LCM has a low oral absorption rate in laying hens, and this was consistent with the findings from the egg residue profiles. Further studies are requested to elucidate the exact reasons for evidently low oral drug absorption in laying hens.


Assuntos
Resíduos de Drogas , Animais , Feminino , Disponibilidade Biológica , Resíduos de Drogas/análise , Lincomicina , Galinhas , Óvulo , Ovos/análise
18.
Heliyon ; 9(11): e22062, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38034622

RESUMO

Cyclophosphamide (CP) is mainly used to treat autoimmune diseases and cancer; however, it damages normal immune cells. Therefore, the effects of chemotherapy on CP are limited. Notably, green tea has been reported to effectively modulate immune function. Here, given the pharmacological properties of green tea, we evaluated the ability of green tea extract (GTE) to restore immunity suppressed by CP in vivo and to activate macrophages in vitro. GTE significantly improved the suppressed immune function, including spleen index and proliferation of spleen T lymphocytes, as revealed by histopathological examination and flow cytometry analysis. Moreover, GTE effectively activated RAW 264.7, as represented by the induction of nitric oxide, reactive oxygen species, and cytokine levels. GTE also increased the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor kappa B in RAW 264.7 cells. In conclusion, GTE ameliorated CP-induced immunosuppression in mice and stimulated immune activity in RAW 264.7 cells, possibly by activating the MAPK signaling pathway. These findings suggest that GTE has the potential to be used as a supplementary agent in chemotherapy for CP.

19.
Bioeng Transl Med ; 8(6): e10589, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-38023706

RESUMO

Encephaloduroarteriosynangiosis (EDAS), an indirect anastomosis procedure, is widely accepted as a primary treatment for moyamoya disease (MMD) to improve collateral blood flow. During surgical intervention, dural fibroblasts (DuF) are thought to produce various proteins that create an angiogenic microenvironment. However, the biophysiological evidence supporting the angiogenic properties of this surgical technique has not been thoroughly elucidated. The purpose of these studies was to determine whether DuF releases pro-angiogenic factors and chemokines and promotes angiogenic properties in human endothelial cells (ECs) under IL-1ß-mediated wound conditions, which are expected to occur during the process of neo-vascularization within the dura mater. Furthermore, a microfluidic chemotaxis platform was implemented to investigate the angiogenic activity of ECs in response to a reconstituted dura model. Transcriptome sequencing revealed that IL-1ß stimulation on DuF induced a significant upregulation of various pro-angiogenic genes, including IL-6, IL-8, CCL-2, CCL-5, SMOC-1, and SCG-2 (p < 0.05). Moreover, compared to ECs cultured in naïve media or naïve DuF media, those exposed to IL-1ß-DuF conditioned media expressed higher mRNA and protein levels of these pro-angiogenic factors (p < 0.001). ECs co-cultured with IL-1ß-DuF also exhibited considerable migration on the microfluidic chemotaxis platform. Furthermore, the chemotactic effects on the ECs were reduced upon neutralization of IL-8 or inhibition of NF-κB signaling. Our findings demonstrate that IL-1ß-DuFs release factors that activate and enhance the angiogenic properties of ECs. These results suggest a potential interaction between DuF and ECs following EDAS for MMD, and these components could be targeted for the development of therapeutic biomarkers.

20.
bioRxiv ; 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37904957

RESUMO

Reach-to-grasp actions are fundamental to the daily activities of human life, but few methods exist to assess individuals' reaching and grasping actions in unconstrained environments. The Block Building Task (BBT) provides an opportunity to directly observe and quantify these actions, including left/right hand choices. Here we sought to investigate the motor and non-motor causes of left/right hand choices, and optimize the design of the BBT, by manipulating motor and non-motor difficulty in the BBT's unconstrained reach-to-grasp task We hypothesized that greater motor and non-motor (e.g. cognitive/perceptual) difficulty would drive increased usage of the dominant hand. To test this hypothesis, we modulated block size (large vs. small) to influence motor difficulty, and model complexity (10 vs. 5 blocks per model) to influence non-motor difficulty, in healthy adults (n=57). We hypothesized that healthy adults with high non-dominant hand performance in a precision drawing task should be more likely to use their non-dominant hand in the BBT. Our data revealed that increased motor and non-motor difficulty led to lower task performance (slower speed), but participants only increased use of their dominant hand only under the most difficult combination of conditions: in other words, participants allowed their performance to degrade before changing hand choices, even though participants were instructed only to optimize performance. These results demonstrate that hand choices during reach-to grasp actions are more stable than motor performance in healthy right-handed adults, but tasks with multifaceted difficulties can drive individuals to rely more on their dominant hand. Statements and Declarations: Dr. Philip and Washington University in St. Louis have a licensing agreement with PlatformSTL to commercialize the iPad app used in this study.

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